Analysis of the PTEN gene sequence indicated that it was likely to re p resent a dual-specificity protein tyrosine phosphatase, however initial investigations found it difficult to demonstrate phosphotyrosine phosphatase activity. Subsequent studies have provided clear evidence that PTEN is really a phospholipid phosphatase with a preference for the 3’-position of phosphatidylinositol (3,4,5) trisphosphate and phosphatidylinositol (3,4) bisphosphate. Both PIP2 a n d PIP3 a re produced by PI 3-kinase, and an increase in plasma membrane associated PIP2 and PIP3 is required for activation of the protein kinase Akt. Recent studies have indicated that activation of Akt suppresses apoptosis in response to growth factor withdrawal, as well as anokiosis. Consistent with a role for PTEN in regulating activation of Akt, fibroblasts derived from PTEN-deficient mouse embryos are resistant to apoptosis. Recent studies suggesting that PTEN expression is lost in numerous tumor cells indicate that loss of PTEN expression or mutation of the lipid phosphatase activity may play a major role in tumorigenesis.
